Dilated Cardiomyopathy
Conditions
Brief summary
Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. About half of patients die or require heart transplantation within 5 years of diagnosis. The medical therapy for DCM with heart failure includes anti-congestive medications and antiplatelet therapy. Those who fail to improve within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive medications. The investigators had conducted precision-medicine-based approach to provide strategic approach as drug repurposing to identify new treatments. The investigators have identified the beneficial effects from a statin, simvastatin, to restore the cardiac contractility. The investigators would further assess the efficacy of simvastatin to improve the cardiac function in patients with DCM.
Detailed description
Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. About half of patients die or require heart transplantation within 5 years of diagnosis. The survival advantage from transplantation is limited, particularly in DCM infants. The medical therapy for DCM with heart failure includes anti-congestive medications and antiplatelet therapy. Those who fail to improve within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive medications. The investigators had conducted precision-medicine-based approach to provide strategic approach as drug repurposing to identify new treatments. The investigators have identified the beneficial effects from a statin, simvastatin, to restore the cardiac contractility in a DCM proband.The initial experience in the proband is promising. Simvastatin is effective in lowing LDL and cholesterol, thereby to improve the outcome of patients with coronary arterial disease, familiar hypercholesterolemia, etc. For children, though the dosage range and the indication remain unclear, it had been used in children with various diseases. Simvastatin had been given in a small cohort of adult DCM. Patients treated with simvastatin had a lower New York Heart Association functional class compared with those receiving placebo. The LVEF also improved in the simvastatin group. The investigators would further assess the efficacy of simvastatin to improve the cardiac function in patients with DCM.
Interventions
DRUGSimvastatin
* Starting dosage: in adult, the dose of simvastatin is 10 mg once daily. In children, the dose is 0.25mg/Kg/day (maximum dose: 10 mg/d). * Target dosage: in adult, the dose of simvastatin is 20 mg once daily. In children, the dose is 0.5mg/Kg/day (maximum dose: 20 mg/d). * The basic anti-congestive medication will be kept as the same. * The dosage may be titrated to a lesser dose by investigators according to the patient's condition.
Sponsors
National Taiwan University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients who have already received anti-congestive medications for at least three months and still have compromised LV function (LVEF \< 45% and the Z score of the LV end-diastolic diameter \> 2.0). * Patients who have persistent or even worsening heart failure after one month of anti-congestive medications. * Patients who have positive family history of dilated cardiomyopathy and have received anti-congestive medications for one week.
Exclusion criteria
* Patients who underwent prior cardiac surgery. Those who received DCM related cardiac surgery, such as mitral valve plasty, for longer than a year are not subject to this restriction. * Patients who had liver / renal dysfunction. * Patients who are pregnant or plan to pregnancy in the period of study. * Patients who are intolerance to simvastatin therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from base line in left ventricular ejection fraction and end-diastolic dimention by cardiac ultrasound. | baseline, 1st month(The 1st month follow-up time tolerates a 0.5-month window ) |
| Change from baseline in N-terminal pro-brain natriuretic peptide level.natriuretic peptide level. | baseline, 3rd month(The 3rd month follow-up time tolerates a 1-month window ) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v3.0 | Up to 24 months | We will check patient's biochemistry profile including, lipid profile, liver function and renal function. Treatment-related adverse events would be assessed by CTCAE v3.0 |
Countries
Taiwan
Outcome results
None listed